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Original Research |

Secondary Gastrointestinal Cancer in Childhood Cancer Survivors: A Cohort Study

Tara O. Henderson, MD, MPH; Kevin C. Oeffinger, MD; John Whitton, MS; Wendy Leisenring, ScD; Joseph Neglia, MD, MPH; Anna Meadows, MD; Catherine Crotty, MPH; David T. Rubin, MD; Lisa Diller, MD; Peter Inskip, ScD; Susan A. Smith, MPH; Marilyn Stovall, PhD; Louis S. Constine, MD; Sue Hammond, MD; Greg T. Armstrong, MD, MSCE; Leslie L. Robison, PhD; and Paul C. Nathan, MD, MSc
[+] Article and Author Information

From University of Chicago, Chicago, Illinois; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Minnesota, Minneapolis, Minnesota; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Memorial Sloan-Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute and Children's Hospital Boston, Boston, Massachusetts; National Cancer Institute, Bethesda, Maryland; The University of Texas M.D. Anderson Cancer Center, Houston, Texas; University of Rochester, Rochester, New York; Nationwide Children's Hospital, Columbus, Ohio; St. Jude Children's Research Hospital, Memphis, Tennessee; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Acknowledgment: The authors thank Eneida Mendonca, MD, PhD, for her assistance with literature review.

Grant Support: By the NCI through grant U24 CA55727 awarded to Dr. Robison. Additional support was provided by the Intramural Research Program of the National Institutes of Health and NCI and by the American Lebanese-Syrian Associated Charities. Dr. Henderson received support from the NCI through grant K07CA134935.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2422.

Reproducible Research Statement:Study protocol, data set, and statistical code: Not available.

Requests for Single Reprints: Tara O. Henderson, MD, MPH, University of Chicago Department of Pediatrics, Section of Hematology, Oncology and Stem Cell Transplantation, 5841 South Maryland Avenue, MC 4060, Chicago, IL 60637; e-mail, thenderson@peds.bsd.uchicago.edu.

Current Author Addresses: Drs. Henderson and Rubin and Ms. Crotty: University of Chicago Department of Pediatrics, Section of Hematology, Oncology and Stem Cell Transplantation, 5841 South Maryland Avenue, MC 4060, Chicago, IL 60637.

Dr. Oeffinger: Departments of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 396, New York, NY 10065.

Mr. Whitton: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, M4-B402, PO Box 19024, Seattle, WA 98109-1024.

Dr. Leisenring: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, D5-360, PO Box 19024, Seattle, WA 98109-1024.

Dr. Neglia: University of Minnesota Cancer Center, Division of Pediatric Hematology/Oncology, Room D 557, Mayo Building/MMC #484, 420 Delaware Street, SE, Minneapolis, MN 55455.

Dr. Meadows: Children's Hospital of Philadelphia, Division of Oncology, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104.

Dr. Diller: Dana-Farber Cancer Institute, Pediatric Oncology, 44 Binney Street, Boston, MA 02115.

Dr. Inskip: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7052, Bethesda, MD 20892-7238.

Ms. Smith and Dr. Stovall: The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Dr. Constine: University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 647, Rochester, NY 14642.

Dr. Hammond: Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205.

Drs. Armstrong and Robison: St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 28105.

Dr. Nathan: The Hospital for Sick Children, Division of Haematology/Oncology, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

Author Contributions: Conception and design: T.O. Henderson, K.C. Oeffinger, W. Leisenring, J. Neglia, A. Meadows, D.T. Rubin, L. Diller, S. Hammond, G.T. Armstrong, P.C. Nathan.

Analysis and interpretation of the data: T.O. Henderson, K.C. Oeffinger, W. Leisenring, D.T. Rubin, L. Diller, P. Inskip, S.A. Smith, L.S. Constine, S. Hammond, G.T. Armstrong, P.C. Nathan.

Drafting of the article: T.O. Henderson, W. Leisenring, J. Neglia, D.T. Rubin, L. Diller, S.A. Smith, G.T. Armstrong, P.C. Nathan.

Critical revision of the article for important intellectual content: T.O. Henderson, K.C. Oeffinger, W. Leisenring, J. Neglia, D.T. Rubin, L. Diller, P. Inskip, L.S. Constine, L.L. Robison, P.C. Nathan.

Final approval of the article: T.O. Henderson, K.C. Oeffinger, W. Leisenring, A. Meadows, D.T. Rubin, L. Diller, P. Inskip, S.A. Smith, L.S. Constine, S. Hammond, G.T. Armstrong, L.L. Robison, P.C. Nathan.

Provision of study materials or patients: T.O. Henderson, J. Neglia, D.T. Rubin, L. Diller.

Statistical expertise: W. Leisenring.

Obtaining of funding: T.O. Henderson, J. Neglia, D.T. Rubin, L.L. Robison.

Administrative, technical, or logistic support: D.T. Rubin, L.L. Robison.

Collection and assembly of data: T.O. Henderson, J. Neglia, D.T. Rubin, S.A. Smith, S. Hammond, G.T. Armstrong, L.L. Robison.


Ann Intern Med. 2012;156(11):757-766. doi:10.7326/0003-4819-156-11-201206050-00002
Text Size: A A A

Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized.

Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors.

Design: Retrospective cohort study.

Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986.

Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis.

Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development.

Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs.

Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest.

Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population.

Primary Funding Source: National Cancer Institute.

Figures

Grahic Jump Location
Figure 1.

Study flow diagram.

* Data set used for calculation of overall cumulative incidence, standardized incidence ratios, and absolute excess risks.

† Data set used for all analyses involving treatment data.

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Figure 2.

Cumulative incidence of GI and colorectal SMN.

CNS = central nervous system; GI = gastrointestinal; HL = Hodgkin lymphoma; NHL = non-Hodgkin lymphoma; SMN = subsequent malignant neoplasm. A. Overall cumulative incidence of GI SMN. B. Cumulative incidence of GI SMN, by abdominal radiation exposure. C. Cumulative incidence of GI SMN, by primary diagnosis. D. Cumulative incidence of colorectal SMN, by abdominal radiation exposure.

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Increased Risk for Gastrointestinal Cancer in Childhood Cancer Survivors

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